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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.107 no.3 Madrid mar. 2015




Penicillamine induced pseudo-pseudoxanthoma elasticum in a patient with Wilson's disease, which role plays the hepatologist?

Pseudo-pseudoxantoma elástico inducido por D-penicilamina en un paciente con enfermedad de Wilson: ¿qué puede hacer el hepatólogo?


Key words: Wilson's disease. D-penicillamin. Toxicity. Adverse effect. Pseudoxanthoma elasticum.

Palabras clave: Enfermedad de Wilson. Penicilamina. Toxicidad. Efecto adverso. Pseudoxantoma elástico.


Dear Editor,

Wilson's disease (WD) is an inherited disorder caused by a mutation in the ATP7B gene that produces copper accumulation in the liver and brain. Clinically, it is characterized by the presence of hepatic (1), neurological and/or neuropsychiatric disease. D- penicillamine is a copper chelator successfully used in the treatment of WD since 1956 (2). Its high therapeutic effectiveness has been undermined by the frequent occurrence of adverse effects.


Case report

A 30-year-old woman diagnosed at the age of 12 of WD with cirrhosis and portal hypertension without neuropsychiatric involvement. She had been treated with D-penicillamine (350 mg. tid, orally administered) since diagnosis. She consulted for loss of skin flexibility, apparition of whitish papules and redundant skin in cervical and axillary region (Fig. 1A). Skin biopsy was performed supporting the diagnosis of pseudo-pseudoxanthoma elasticum (PPXE) secondary to long term D -penicillamine treatment (Fig. 1 B and C). Treatment with D-penicillamine was discontinued and zinc acetate (50 mg. tid, orally administered) was started. Examination of the ocular fundus and echocardiography was performed to rule out involvement of the elastic tissue at these organs, being the study negative.




According to the latest clinical practice guidelines of the European Association for the Study of the Liver (EASL) (3), the initial treatment of WD are chelating agents such as D-penicillamine, which increase the urinary excretion of copper. Approximately 50 % of patients will develop adverse effects in the first 6 months of treatment and up to a third of them will stop the treatment for this reason (4). Half of the patients treated with D-penicillamine have skin lesions, frequently characterized by the alteration of elastic fibers: PPXE, elastosis perforans serpinginosa, cutis laxa, and anetoderma. Several of these entities may coexist in the same patient (5). PPXE is characterized by the appearance of small yellowish papules in the sides of the neck and flexures. Over time, the skin may become lax forming redundant folds (6). Histologically, the PPXE is defined by the appearance of small, frayed and intensely basophilic elastic fibers in superficial reticular dermis. Specific stains for elastic tissue, as orcein show elastic fibers with irregular excrescences. Elastic fibers from other tissues and organs (7) (retina, lung, cardiovascular system...) may also be affected, so examination of the ocular fundus (8) and echocardiography (9) is recommended. If the patient presents dyspnea, it is recommended to perform radiography/chest CT, arterial gasometry and spirometry.

In the presence of a D-penicillamine-associated dermatosis, it is recommended to replace D-penicillamine for trientine or inhibitors of the intestinal absorption of copper (3): Ammonium tetrathiomolybdate or zinc salts. The resolution of PPXE after the change of treatment may take several years to correct due to the slow turnover of the elastic fibers. There is no medical treatment to expedite the resolution of the skin lesions and recover the elasticity (10). In our patient, treatment with zinc acetate was initiated without incidents. A year later the skin lesions persisted unchanged and liver disease was suitably controlled.


Luis Ibáñez-Samaniego, Alejandra Ochoa-Palominos,
María Vega Catalina-Rodríguez, Magdalena Salcedo-Plaza
and Gerardo Clemente-Ricote

Liver Unit. Hospital General Universitario
Gregorio Marañón. Madrid, Spain



1. Ochoa Palominos A, Ibáñez Samaniego L, Catalina Rodríguez MV, Pajares Díaz J, Clemente Ricote G. Wilson's disease: Clinical spectrum of liver disease. Gastroenterol Hepatol 2013;36:86-91.         [ Links ]

2. Walshe JM. Penicillamine, a new oral therapy for Wilson's disease. Am J Med 1956;21:487-95.         [ Links ]

3. European Association for Study of Liver. EASL Clinical Practice Guidelines: Wilson's disease. J Hepatol 2012;56:671-85.         [ Links ]

4. Shiokawa Y, Horiuchi Y, Honma M, Kageyama T, Kageyama T, Okada T, et al. Clinical evaluation of D-penicillamine by multicentric double-blind comparative study in chronic rheumatoid arthritis. Arthritis Rheum 1977;20:1464-72.         [ Links ]

5. Bécuwe C, Dalle S, Ronger-Savlé S, Skowron F, Balme B, Kanitakis J, et al. Elastosis perforans serpiginosa associated with pseudo-pseudoxanthoma elasticum during treatment of Wilson's disease with penicillamine. Dermatology 2005;210:60-3.         [ Links ]

6. Rodríguez Peralto JL, Saiz A, Galera C. Seudoxantoma elástico. En: Herrera Ceballos E, Moreno Carazo A, Requena Caballero L, Rodríguez Peralto JL, editores. Dermatopatología: correlación clínico-patológica. Barcelona: Menarini; 2007. p. 575-7.         [ Links ]

7. Coatesworth AP, Darnton SJ, Green RM, Cayton RM, Antonakopoulos GN. A case of systemic pseudo-pseudoxanthoma elasticum with diverse symptomatology caused by long-term penicillamine use. J Clin Pathol 1998;51:169-71.         [ Links ]

8. Georgalas I, Tservakis I, Papaconstaninou D, Kardara M, Koutsandrea C, Ladas I. Pseudoxanthoma elasticum, ocular manifestations, complications and treatment. Clin Exp Optom 2011;94:169-80.         [ Links ]

9. Campens L, Vanakker OM, Trachet B, Segers P, Leroy BP, De Zaeytijd J, et al. Characterization of cardiovascular involvement in pseudoxanthoma elasticum families. Arterioscler Thromb Vasc Biol 2013;33:2646-52.         [ Links ]

10. Ratnavel RC, Norris PG. Penicillamine-induced elastosis perforans serpiginosa treated successfully with isotretinoin. Dermatology 1994;189:81-3.         [ Links ]

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